Here, a human organotypic microphysiological system (MPS) was presented that includes endothelial-like cells, pericytes, glia, and cortical neurons and maintains blood-brain-barrier (BBB) permeability at in vivo relevant levels. This human Brain-Chip is engineered to recapitulate critical aspects of the complex interactions that mediate neuroinflammation and demonstrates significant improvements in clinical mimicry compared to previously reported similar MPS. In comparison to Transwell culture, the transcriptomic profiling of the Brain-Chip displayed significantly advanced similarity to the human adult cortex and enrichment in key neurobiological pathways. Exposure to TNF-α recreated the anticipated inflammatory environment shown by glia activation, increased release of proinflammatory cytokines, and compromised barrier permeability. In summary, the development of a robust brain MPS for the mechanistic understanding of cell-cell interactions and BBB function during neuroinflammation was reported.
A microengineered brain-chip to model neuroinflammation in humans
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